Table 2.
Pharmacokinetic parameters of OH-voriconazole and DiOH-voriconazole after oral and intravenous administration of a single 400 mg dose of voriconazole to 20 healthy participants; the data are sorted according to the CYP2C19 genotypes
| OH-VRZ | OH-VRZ | DiOH-VRC | DiOH-VRZ | ||||||
|---|---|---|---|---|---|---|---|---|---|
| i.v | Oral | i.v. | Oral | ||||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | ||
| EM | n= 8 | ||||||||
| Cmax | nmol ml−1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.2 | 0.1 | 0.2 | 0.1 |
| Tmax | h | 27.8 | 4.4 | 15.3 | 12.8 | 27.8 | 4.4 | 23.5 | 6.3 |
| t1/2 | h | 14.3 | 6.4 | 31.6 | 35.5 | 17.5 | 5.5 | 25.8 | 25.1 |
| AUC | h nmol−1 ml−1 | 3.5 | 1.0 | 3.4 | 1.3 | 5.6 | 1.4 | 6.4 | 2.1 |
| MRT | h | 33.7 | 7.9 | 55.4 | 48.6 | 38.7 | 8.0 | 48.5 | 35.9 |
| F | % | 95.0 | 18.2 | 113 | 23.6 | ||||
| HEM | n= 8 | ||||||||
| Cmax | nmol ml−1 | 0.1a | 0.04 | 0.1 | 0.03 | 0.1 | 0.07 | 0.1 | 0.04 |
| Tmax | h | 24.0 | 9.6 | 23.0 | 13.6 | 25.8 | 8.3 | 18.4 | 13.5 |
| t1/2 | h | 22.1 | 8.8 | 22.3 | 7.8 | 28.0 | 11.3 | 24.5 | 12.0 |
| AUC | h nmol−1 ml−1 | 2.9 | 1.2 | 3.0 | 0.7 | 5.3 | 2.4 | 5.0 | 0.9 |
| MRT | h | 42.7 | 13.9 | 44.2 | 12.9 | 50.7 | 14.7 | 47.6 | 15.6 |
| F | % | 107 | 23.0 | 113 | 59.5 | ||||
| PM | n= 4 | ||||||||
| Cmax | nmol ml−1 | 0.1 | 0.02 | 0.1 | 0.03 | 0.1 | 0.1 | 0.1 | 0.1 |
| Tmax | h | 21.3 | 13.2 | 15.8 | 15.6 | 23.4 | 14.4 | 16.1 | 15.3 |
| t1/2 | h | 19.5 | 3.0 | 28.9 | 12.2 | 16.8 | 1.1 | 25.9 | 10.1 |
| AUC | h nmol−1 ml−1 | 2.9 | 1.4 | 3.4 | 1.2 | 6.4 | 2.5 | 5.9 | 2.8 |
| MRT | h | 40.3 | 3.1 | 52.7 | 18.2 | 37.7 | 2.6 | 49.2 | 13.3 |
| F | % | 127 | 30.3 | 91.3 | 8.9 | ||||
a
*1/*1 vs.*1/*2 P < 0.05. EM, extensive metabolizers; MRT, mean residence time; HEM, heterozygous extensive metabolizer; PM, poor metabolizers.